X-ray diffraction, electron microscopy, and biochemical procedures will be used to study multisubunit enzymes that are of central importance in regulation of metabolism. Our objectives are: (1) To determine the three-dimensional organization of glutamine synthetase, and to interpret its complex regulatory and catalytic function in terms of structure; (2) To determine the atomic structure of ribulose-1, 5-bisphosphate carboxylase, the most abundant protein on earth; (3) To complete a study of the structure of aldolase and to interpret its structure in terms of its mechanism. One long-range goal is to provide the basis for understanding normal and pathological metabolism at the molecular level. The above enzymes have been selected because their complexity offers the possibility that new principles of regulation may emerge from studies of them. At the same time, they are not sufficiently well characterized that x-ray diffraction and other biophysical tools can be applied to them.